Cell-to cell interactions and metabolic cooperation will be further studied in monolayer cultures of pancreatic islet cells, via microinjection of a fluorochrome (i.e., Lucifer Yellow) better tolerated than previously used 6-carboxyfluorescein, also via dual injections of metabolites (glucose-6-phosphate, lactate, malate) and modifiers (adenine nucleotides, Ca ions). "Communication territories" are identified by fluorescence photography and the kinetics of intercellular communication are evaluated by mutichannel microfluorometry. Transition from one- to two-dimensional fluorescence scans will allow complete topographic and kinetic analysis of fluorochrome transfer, or NAD(P)H and flavin oxidoredox transients due to injected substrate. Injected clusters are retrieved for electron microscopy or immunofluorescence studies. Tailored computer programs allow detailed analysis of cell-to-cell passage at high time resolution and at any point in the communicating territory. Present results indicate the influence of glucose, intra-extra-cellular Ca ions, drugs (isomethyl butyl xanthine) and hormones (somatostatin) on islet cell communication. In most cases communicating territories are no larger than 2-5 cells, with rare instances of massive communication. While communication is absent or delayed in very low glucose levels (0 to 0.25 mM), in the 3.3 to 16.7 mM range the differences are discrete in terms of communicating cell numbers. Even though most of the communication is observed from B to B cell, retrieval studies indicate some instances of B to A or B to D communication. Hitherto unknown phenomena such as oscillatory shifts of oxidoredox states, with opposite states in neighboring cells are also unraveled. Current and future goals include topographic kinetic studies with metabolites, ions, hormones and agents such as somatomedin which interact with hormone receptors. Progressing from photographic delimitation of communicating territories to a dynamic analysis of such territories, structure and function studies will be pursued on the regulation of islet cells and their responses to secretagogues or ultimately potential therapeutic agents.